Glock began racing in 1998 at age fifteen. He won several karting championships, the BMW ADAC Formula Junior Cup in 2000, and the Formula BMW ADAC championship in 2001. He progressed to the German Formula Three Championship in 2002, finishing third and earning rookie of the year honours. In the 2003 Formula Three Euroseries he won three races and placed fifth in the championship.
Glock was signed as Jordan Grand Prix's test driver for the 2004 season and made his race debut at the Canadian Grand Prix, replacing Giorgio Pantano amid a contract dispute. He finished eleventh but inherited seventh after the disqualification of the Williams and Toyota cars, scoring two points on debut. He remained with Jordan for the final three races of the season.
In 2005, Glock moved to the United States to race in the Champ Car World Series with Paul Gentilozzi's Rocketsports team. His best finish was second at Montreal's Circuit Gilles Villeneuve, though he was asked by officials to cede the lead after retaining position by running off-track. He finished eighth in the final points standings and won the Champ Car Rookie of the Year award.
Glock returned to Europe for the GP2 Series in 2006, starting with BCN Competicion before moving mid-season to iSport, where he recovered to fourth in the championship and won the most-improved-driver award. He re-signed with iSport for 2007 and won one feature race and four sprint races on his way to the GP2 championship title, making him a clear candidate for a Formula One return.
Glock signed a three-year contract with Toyota F1 for 2008. He scored points in Canada, then qualified a career-best fifth at the Hungarian Grand Prix and finished second. At Singapore he finished fourth. He ended the year tenth in the Drivers' Championship with 25 points.
The defining moment of Glock's career came at the final race of the 2008 season in Sao Paulo. Running on dry-weather tyres as rain began to fall in the closing laps, Glock stayed out while most rivals pitted for wet tyres. He was passed by Sebastian Vettel and Lewis Hamilton in the final corners of the final lap, allowing Hamilton to take fifth place — and with it the Drivers' Championship by one point over Felipe Massa. The Brazilian fans directing blame at Glock prompted the Toyota team to arrange a police escort to leave the country safely. Commentator Martin Brundle's exclamation "Is that Glock going slowly?" during live ITV coverage became a recurring internet meme.
Glock had a strong early 2009 season. He qualified sixth for the Australian opener before a rear wing legality ruling moved him to nineteenth, from which he recovered to finish fourth. In Malaysia, inspired tyre strategy in wet conditions brought him third place when the race ended early under red flags. He earned his second podium of the season at Singapore, finishing second behind Hamilton. At the Japanese Grand Prix, Glock qualified well but crashed heavily at the final corner and was airlifted to hospital with a leg injury, later found to include a cracked vertebra. Toyota withdrew from Formula One at the end of 2009.
Glock signed with the new Manor Grand Prix team, which became Virgin Racing, as their lead driver for 2010 and 2011. The team was consistently among the slowest on the grid. His best result in 2010 was fourteenth in Japan. In 2011 Jerome d'Ambrosio joined as his teammate, and Glock signed a three-year contract extension. The team was renamed Marussia for 2012. Despite a difficult car, Glock produced his best result for the team at Singapore 2012, finishing twelfth and pushing Marussia ahead of Caterham in the Constructors' Championship — a meaningful result in the battle for tenth place. He departed the team by mutual consent in January 2013.
Glock joined BMW for the 2013 Deutsche Tourenwagen Masters season as a factory driver. He scored his first DTM points with a third-place finish in his third race and claimed his maiden DTM victory at the season finale at Hockenheim. He continued in the DTM for multiple seasons as a BMW factory representative.
From 2018 to 2020, Glock worked as a pundit for RTL's German-language Formula One television coverage. From 2021 onwards he joined Sky Sport Germany as a Formula One analyst after the broadcaster acquired exclusive German rights to the sport. He lives in Switzerland with his wife, German model Isabell Reis.